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  • 1
    ISSN: 1432-1106
    Keywords: 6-OHDA lesion ; Foetal ventral mesencephalic graft ; L-DOPA and carbidopa ; Parkinson's disease ; Circling behaviour ; Neural grafting ; Gliosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats with a unilateral 6-OHDA lesion of the nigrostriatal pathway, foetal ventral mesencephalic grafts implanted into the 6-OHDA-lesioned striatum produced a reduction in apomorphine-induced contralateral rotation, and complete abolition of (+)-amphetamine-induced ipsilateral rotation. The graft-induced reduction of apomorphine and (+)-amphetamine-induced rotation was not affected by chronic 27 week administration of L-DOPA and carbidopa to rats receiving foetal grafts. TH-immunohistochemistry revealed 〉96% loss of dopamine cells in the substantia nigra ipsilateral to the 6-OHDA lesion in all animals, but cell loss in the ipsilateral ventral tegmental area was more variable (21–46% of the intact side). TH-positive cells in the intact substantia nigra and ventral tegmental area were not affected by chronic treatment with L-DOPA and carbidopa. In the lesioned striatum of rats receiving sham grafts, no TH-positive cells or fibres were seen. In the 6-OHDA-lesioned striatum of animals receiving foetal grafts, many TH-positive cells were seen in the grafts and chronic treatment with L-DOPA and carbidopa did not reduce cell survival. GFA-P immunohistochemistry revealed that a unilateral 6-OHDA lesion followed by a sham graft was not associated with a reactive gliosis reaction in the striatum at the time of study (38 weeks after lesion surgery and 30 weeks after sham-graft), and treatment of such rats with L-DOPA and carbidopa was also without effect on glia. In contrast there was a marked gliosis in the striatum surrounding foetal grafts which was unaffected by chronic treatment with L-DOPA and carbidopa. The grafts themselves were surrounded by a rim of glial cells, and the glial density within the grafts was higher in animals receiving chronic L-DOPA and carbidopa treatment. However, there was no obvious relationship between the number of TH-positive cells within the grafts, or graft volume, and glial cell density within the grafts. These results suggest that long-term treatment with L-DOPA and carbidopa does not impair either the behavioural recovery produced by foetal ventral mesencephalic grafts in rats or the long-term survival of grafts as revealed by TH-immunohistochemistry. The presence of a foetal graft is associated with a reactive gliosis in the implanted striatum, which was not altered by long-term treatment with L-DOPA and carbidopa. However such treatment did result in an increase in glial density within the grafts themselves.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Partial lesion ; 6-OHDA ; PET
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lesion caused by a single 6-hydroxydopamine injection into rat striatum was evaluated. In vivo positron emission tomography using a dopamine reuptake tracer revealed no consistent reduction in striatal dopamine transporter. Amphetamine rotation test was negative up to 18 weeks. A 21% reduction in striatal dopamine seen at 11 weeks was not detectable at 18 weeks. Tyrosine hydroxylase-positive neurone counts showed no decline in substantia nigra. Our results suggest that this lesion may be subject to compensation and therefore should be used with caution in studies on neuroprotective treatments of Parkinson' disease.
    Type of Medium: Electronic Resource
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